ADP-A2M10 Dose-Escalation Trial in MAGE-A10–Positive Urothelial Tumors
Posted: Tuesday, December 15, 2020
David Hong, MD, of MD Anderson Cancer Center, Houston, and colleagues conducted a dose-escalation trial with ADP-A2M10 T cells, which express a high-affinity MAGE-A10–specific T-cell receptor targeting MAGE-A10–positive urothelial tumors in the context of HLA A*02. Their work was presented at the 2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 285) and published in the Journal for ImmunoTherapy of Cancer.
A modified 3+3 design was used for this ADP-A2M10 dose-escalation trial to evaluate antitumor activity and safety. A total of 10 patients were enrolled in the study, all HLA A*02–positive with tumors expressing MAGE-A10, and all had urothelial cancer, melanoma, or advanced head and neck squamous cell carcinoma. Participants underwent apheresis, and their T cells were isolated, transduced with the MAGE-A10 TCR-containing vector, and expanded. Lymphodepletion with fludarabine and cyclophosphamide was administered before receiving ADP-A2M10, administered at two doses—0.1 × 109 and > 1.2–6 × 109—and the dose expansion was 1.2–15 × 109 transduced cells.
Of the enrolled, three patients were treated with both doses, and four patients were treated in the dose-expansion phase. ADP-A2M10 T cells were detected in peripheral blood samples from patients at each dose level and in tumor tissues from several points during dose expansion. Neutropenia, leukopenia, anemia, thrombocytopenia, and lymphopenia of grade 3 or higher occurred most frequently. Cytokine-release syndrome with resolution was reported in two patients. Stable disease and progressive disease occurred in three and five patients, respectively.
Disclosure: For full disclosures of the study authors, visit jitc.bmj.com.